Pediatric Endocrinology Sarah Lawrence Division of Endocrinology CHEO

Outline Growth/short stature Puberty – precocious and delayed Disorders of Sex Development Diabetes Thyroid

Short Stature

Predicted Height 177 cm 168 cm 155 cm 3 boys age 10 128 cm BA 8 BA 10 BA 12 Which will be taller as an adult? 177 cm 168 cm 155 cm

Midparental [target] height: males Father Target Height Mother

Midparental [target] height: females Father Target Height Mother

Endocrinopathy Based on this growth chart, what is the MOST likely cause of this boy’s growth failure? Primary hypothyroidism Craniopharyngioma Down Syndrome Inflammatory Bowel disease Scoliosis

Chronic Disease Based on this growth chart, what is the MOST likely cause of this boy’s growth failure? Primary hypothyroidism Craniopharyngioma Down Syndrome Inflammatory Bowel disease Scoliosis

Approach to Short Stature Growth velocity Target Height Normal Variant Pathologic Familial Short Stature Constitutional Delay Proportionate Disproportionate Prenatal Postnatal Idiopathic Short Stature IUGR Medications Dysmorphic syndromes Chronic disease Chromosomal disorders Endocrine

Precocious Puberty Presence of secondary sexual development by age: 8 in a girl 9 in a boy

Puberty Sequence: Girls

Puberty Sequence: Males

Approach to Precocious Puberty Growth Velocity Bone Age Normal Increased Normal variant Pathological Estrogen Androgens Central Peripheral Premature Thelarche Premature Adrenarche Androgens Estrogen

Question A 6 year old girl presents with pubic hair, axillary hair and odour and mild acne. Her growth is as shown. What is the MOST likely cause of her precocious puberty? Congenital adrenal hyperplasia Benign premature thelarche Benign premature adrenarche Adrenal tumour Central precocious puberty

Question A 6.5 year old girl presents with a 10 month history of breasts and pubic hair. What is the MOST likely cause? Benign premature thelarche Congenital adrenal hyperplasia Craniopharyngioma Ovarian tumour Idiopathic central precocious puberty

Approach to Precocious Puberty: Females Bone age, GV Normal Increased Normal Variant Pathological Estrogen Androgens Central Peripheral Premature Premature Estrogen Estrogen Androgens Thelarche Adrenarche +/- androgens Ovary Ovary Adrenal Adrenal Other Other

CAH 29/01/92 Question A 5 year old boy presents with pubic hair, growth acceleration. He has Tanner 4 pubic hair and genitalia with 2 ml testes. What is the MOST likely diagnosis? Idiopathic central puberty Congenital adrenal hyperplasia Hypothalamic tumour Testicular tumour x

Approach to Precocious Puberty: Males Bone age, GV Normal Increased Normal Variant Pathological Androgens Central Peripheral Premature Testes > 4ml Androgens Estrogen Adrenarche Testes Testes Adrenal Adrenal Other Other

Delayed Puberty Absence of secondary sexual development by age: 13 in a girl 14 in a boy

Approach to Delayed Puberty LH, FSH Low High Central Peripheral Constitutional Delay Hypothalamic or Gonadal Failure of Growth and Puberty Pituitary Cause

Delayed Puberty: Investigations Growth records Bone age LH, FSH Sex hormone levels - not needed Other hormones as clinically indicated (T4, TSH, GH, Prolactin, Cortisol)

Delayed Puberty: Treatment Hyper / Hypogonadotropic Hypogonadism Boys: Testosterone intramuscular injection, transdermal patch/gel or orally, gradually increasing to adult doses Girls: Start with low dose estrogen, increasing over 1-2 years, then begin cycling with estrogen and progesterone

Ambiguous Genitalia (Disorders of Sex Development) 46 XY 46 XX 46 XY 46 XY

Development of Internal and External Genitalia http://www.aboutkidshealth.ca/En/HowTheBodyWorks/SexDevelopmentAnOverview/Pages/default.aspx

Approach to Disorders of Sex Development Gonads palpable No Unilateral Bilateral Probable virilized female 46 XX DSD Hypospadias Undervirilized male 46 XY DSD Ovotesticular DSD Maternal Fetal Hormonal Hypospadias Mixed Gonadal Likely CAH Testosterone Dysgenesis Synthesis Defect 5-a-reductase deficiency Androgen Insensitivity Syndrome (AIS) Genetic syndrome

Type 1 Diabetes

Epidemiology of Type 1 Prevalence 0.4% of individuals < 18 years Increased risk to family members Sibling 5% Father with diabetes 6-8% Mother with diabetes 2-3% Identical twin 30-50%

Diagnostic Criteria FBG > 7.0 mmol/L OR Casual BG > 11.1 with symptoms OR 2 hour BG in OGTT of > 11.1 Pediatrics: do not need confirmatory sample on another day in the presence of unequivocal hyperglycemia and symptoms.

Premeal target (mmol/L) BG Targets Age (years) Premeal target (mmol/L) HbA1c Target (%) < 5 6-12 < 8.5% 4-10 < 8.0% >12 4-7 < 7.0%

DKA: How common is it? At diagnosis of diabetes Established diabetes 15-67% present with DKA Established diabetes 1-10% of patients/year Cerebral edema 0.4-1% of episodes of DKA 25% mortality, up to 35% with severe neurologic deficits

Cerebral Edema in DKA Who is at risk? Increased risk in new onset DM, more dehydrated and acidotic patients ?treatment factors – rapid infusion of hypo-osmolar fluids, use of bicarbonate Treatment – early intervention is key Raise HOB, + intubate, reduce fluids hypertonic saline, mannitol

DKA: What you need to remember The best way to prevent CE-DKA is to prevent DKA How do you prevent cerebral edema once child presents in DKA? By remembering a few guiding principles: The younger the child, the greater the risk No insulin bolus No fluid bolus, unless in shock (max 10 cc/kg over 20-30 minutes)

Question: An 8 yo girl is diagnosed with Type 1 diabetes. At what age should you begin screening for: Microalbuminuria Retinopathy Hypothyroidism Hyperlipidemia Celiac disease

Complication Screening Who When How Nephropathy 12 yo and DM>5 years Annual Albumin/creatinine ratio Retinopathy >15 yo and DM >5 years Opthalmoscopy/ fundus photography Neuropathy Post pubertal, poor control, DM>5 years Symptoms, Sensory exam Dyslipidemia All + targeted Age 12, 17 Fasting lipid profile Hypertension All Twice annual BP measurement Thyroid Dx + q1-2y TSH, TAB Celiac Targeted Symptoms TTG, IgA

Type 2 Diabetes in Children and Youth

Presentation of T1DM vs T2DM Type 1 Type 2 Up to ¼ overweight Short Course 15-40% DKA FHx T1DM in 5-10% Predominantly white 85% overweight Indolent course 33% ketonuria 5-25% DKA FHx T2DM 74-100% Minority youth

Acanthosis Nigricans

For Children, BMI Changes with Age Boys: 2 to 20 years Example: 95th Percentile Tracking Age BMI 2 yrs 19.3 4 yrs 17.8 9 yrs 21.0 13 yrs 25.1 BMI changes substantially with age. After about 1 year of age, BMI-for-age begins to decline and it continues falling during the preschool years until it reaches a minimum around 4 to 6 years of age. Here you see BMI-for-age tracking on the 95th percentile. BMI BMI

Genetic and Environmental Risk factors for T2DM Ethnicity Female gender Family history T2DM Intrauterine factors Maternal history of gestational diabetes Large for gestational age (>4 kg) Small for gestational age (<2.5 kg) Obesity Sedentary behaviour

Question A 13 year old boy with a BMI of 30, acanthosis nigricans, and a family history of Type 2 diabetes presents with a random glucose of 15 mmol/L, negative ketones. A What is the medication of first choice? B What is the target A1c?

Treatment of T2DM in Youth Diabetes education for the family Setting glycemic targets HbA1c < 7.0% Lifestyle modification <10% achieve glycemic targets Pharmacotherapy Metformin has been shown to have short term efficacy and safety in adolescents Insulin rescue is required in those with severe metabolic decompensation at diagnosis e.g. DKA, A1C ≥9.0%, symptoms of severe hyperglycemia, ketonuria

Thyroid Disorders

Approach to Goitre Goitre TSH Elevated Normal Suppressed Hypothyroid Euthyroid Hyperthyroid Thyroid Antibodies Thyroid Antibodies Thyroid Antibodies +ve -ve +ve -ve Grave's disease, Chronic lymphocytic Goitrogen, Chronic lymphocytic Colloid goitre Subacute thyroiditis Toxic nodule thyroiditis Dyshormonogenesis thyroiditis

Thyroid take home points Thyroid disorders are common in children and adolescents Most commonly present with goitre secondary to autoimmune thyroiditis or a simple colloid goitre TSH and thyroid antibodies is usually all that is required to establish the diagnosis

Thyroid take home points Mild elevations of TSH should be verified on repeat testing TSH <10mU/L often normal on repeat Routine monitoring – q6 months while growing, q year once adult height Natural history studies suggest a high rate of spontaneous resolution with autoimmune thyroid disease and thus, repeat testing should be done before committing to lifelong thyroid hormone replacement

Thyroid take home points Congenital hypothyroidism detected through newborn screening – they need more intensive monitoring particularly in the 1st 3 years of life

Questions?